What is the information about Repatha (Evolocumab)?

From the Guidelines

Repatha (evolocumab) is a highly effective medication for lowering LDL cholesterol in adults with high cholesterol, particularly those with familial hypercholesterolemia or established cardiovascular disease, and should be considered as an adjunct to diet and maximally tolerated statin therapy in patients who require additional lowering of LDL cholesterol, as evidenced by the FOURIER trial which demonstrated a 59% reduction in LDL cholesterol and a 15% relative risk reduction in major cardiovascular events 1.

Key Points

• Repatha is a PCSK9 inhibitor that works by helping the liver remove more LDL cholesterol from the bloodstream
• It is typically administered as a subcutaneous injection, available in either a 140 mg dose given every two weeks or a 420 mg dose given monthly
• Common side effects include injection site reactions, upper respiratory infections, flu-like symptoms, back pain, and muscle pain
• Repatha is generally used when statins alone are not effective enough or cannot be tolerated
• It is essential to continue any prescribed diet and exercise program while taking Repatha, as the medication works best as part of a comprehensive approach to cholesterol management

Administration and Dosage

• Repatha is administered via subcutaneous injection in the thigh, abdomen, or upper arm
• The recommended dose is 140 mg every two weeks or 420 mg once monthly
• Patients should be trained on how to self-administer the medication at home

Indications and Contraindications

• Repatha is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with primary hyperlipidemia, including those with familial hypercholesterolemia or established cardiovascular disease
• There are no known contraindications to Repatha, but patients with a history of hypersensitivity to the medication should not use it

Monitoring and Follow-up

• Regular blood tests will be needed to monitor cholesterol levels and assess the medication's effectiveness
• Patients should inform their healthcare provider about all medications they're taking and any allergies or medical conditions they have before starting Repatha
• The medication's effectiveness and potential side effects should be closely monitored, and adjustments to the treatment plan should be made as needed.

From the FDA Drug Label

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use REPATHA® safely and effectively. See full prescribing information for REPATHA. REPATHA (evolocumab) injection, for subcutaneous use Initial U.S. Approval: 2015 RECENT MAJOR CHANGES Indications and Usage (1)11/2024 Dosage and Administration (2.3)11/2024 Warnings and Precautions (5. The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously. In adults with established CVD or with primary hyperlipidemia: In pediatric patients aged 10 years and older with HeFH: In adults and pediatric patients aged 10 years and older with HoFH: The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously. The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks. Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete. Assess LDL-C when clinically appropriate. The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation. REPATHA is available as prefilled single-dose SureClick® autoinjectors and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex. Consider prescribing a presentation of REPATHA that does not contain dry natural rubber for individuals that are sensitive to latex. Administer REPATHA subcutaneously into areas of the abdomen, thigh, or upper arm. Rotate injection sites for each administration. Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). Evolocumab has an approximate molecular weight (MW) of 144 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells REPATHA is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution for subcutaneous use. Each 1 mL prefilled single-dose SureClick® autoinjector and prefilled single-dose syringe contains 140 mg evolocumab, acetate (1.2 mg), polysorbate 80 (0.1 mg), proline (25 mg) in Water for Injection, USP. Sodium hydroxide may be used to adjust to a pH of 5. 0. Each single-dose Pushtronex® system (on-body infusor with prefilled cartridge) delivers a 3.5 mL solution containing 420 mg evolocumab, acetate (4.2 mg), polysorbate 80 (0.35 mg), proline (89 mg) in Water for Injection, USP. Sodium hydroxide may be used to adjust to a pH of 5.0.

Key Points:

• Indications: REPATHA is used to reduce LDL-C in adults with established cardiovascular disease, primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), and homozygous familial hypercholesterolemia (HoFH).
• Dosage: The recommended dosage is 140 mg every 2 weeks or 420 mg once monthly, administered subcutaneously.
• Administration: REPATHA is available as prefilled single-dose autoinjectors and syringes, and should be administered into areas of the abdomen, thigh, or upper arm, rotating injection sites for each administration.
• Mechanism of Action: Evolocumab is a human monoclonal IgG2 directed against human proprotein convertase subtilisin kexin type 9 (PCSK9), which increases the number of LDL receptors available to clear LDL from the blood, thereby lowering LDL-C levels.
• Pharmacokinetics: Evolocumab exhibits non-linear kinetics, with a half-life of 11 to 17 days, and is primarily eliminated through a non-saturable proteolytic pathway. 2 2 2

From the Research

Overview of Repatha (Evolocumab)

• Repatha (evolocumab) is a monoclonal antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) to lower low-density lipoprotein cholesterol (LDL-C) levels 3.
• It is administered subcutaneously at a dosage of 140 mg every 2 weeks or 420 mg once monthly 3.

Efficacy in Lowering LDL-C Levels

• Evolocumab has been shown to be effective in reducing LDL-C levels by approximately 60% in patients at high risk for atherosclerotic cardiovascular disease already taking maximal statin therapy 4.
• In patients with primary hypercholesterolemia or mixed dyslipidemia, evolocumab reduced LDL-C levels by 54.8 to 76.3% compared to placebo, and by 36.9 to 47.2% compared to ezetimibe 3.
• In patients with homozygous familial hypercholesterolemia, evolocumab reduced LDL-C levels by approximately 30% compared to placebo when added to statins with or without ezetimibe 3.

Safety and Tolerability

• Evolocumab has been shown to be well tolerated, with balanced rates of adverse events leading to discontinuation of evolocumab compared to placebo and/or ezetimibe 5.
• The most common adverse reactions reported with evolocumab include allergies, myalgia, poor blood glucose control, and liver damage 6.

Use in Specific Patient Populations

• Evolocumab has been shown to be effective in patients with extremely high-risk acute coronary syndrome, reducing LDL-C levels by approximately 70% and improving cardiovascular prognosis 6.
• In patients with mixed hyperlipidemia, evolocumab reduced LDL-C levels by approximately 67% compared to placebo, and by 42% compared to ezetimibe 5.
• Evolocumab has also been shown to be effective in patients with acute coronary syndromes, reducing LDL-C levels by approximately 40% and achieving LDL-C target levels in over 95% of patients 7.